Nalmefene
Treatment of alcohol use disorder in patients with an average daily alcohol consumption of >60g for men and >40g for women, who have failed psychosocial intervention for at least 2 weeks, with the goal of reduction in alcohol consumption.
Decision on record
- Meeting Nov 2015 Not recommended Alcohol dependence
From the public summary
7.1 The PBAC did not recommend the listing of nalmefene for the treatment of alcohol dependence. In reaching this conclusion, the PBAC considered that the clinical place of therapy was not well defined and therefore the comparator was uncertain. The PBAC also considered that it was not clear whether the demonstrated effect was clinically meaningful.PSD · Nov 2015
7.2 The PBAC considered that the clinical place in therapy was unclear and considered that consultation with hepatologists and addiction specialists may assist in determining the most appropriate clinical place for nalmefene.PSD · Nov 2015
6.27 The submission presented two economic evaluations: a modelled economic evaluation based on the results of the post-hoc subgroup analysis of patients with high to very high drinking levels from the pivotal placebo- controlled nalmefene trials; and a cost-minimisation analysis of nalmefene versus naltrexone based on the submission’s informal indirect analysis.PSD · Nov 2015
6.28 The results of the two economic evaluations were combined to justify the price for nalmefene, with the proposed price a weighted average of the two prices, assuming one-third of patients treated with nalmefene would otherwise receive naltrexone. No justification was provided for this assumption. Given the large difference in price for nalmefene depending on comparator, this has a substantial impact on the weighted price of nalmefene.PSD · Nov 2015
6.22 The submission described nalmefene as superior in terms of comparative effectiveness and inferior in terms of comparative safety over placebo (in combination with a psychosocial intervention). This claim was adequately supported in terms of safety, but poorly supported in terms of efficacy for the overall population (full analysis set) and only partially supported in the target population (i.e.PSD · Nov 2015
6.23 The submission described nalmefene as non-inferior in terms of comparative effectiveness and safety compared to naltrexone (in combination with a psychosocial intervention). This claim was not adequately supported. The nalmefene and naltrexone trials presented in the submission were not comparable due to differences in trial design, population, dose regimens, outcomes and severity of alcohol dependence.PSD · Nov 2015
6.53 The sponsor indicated willingness to negotiate a risk share arrangement, and proposed an aggregate spending cap that would manage the risk of utilisation of nalmefene outside the proposed PBS restrictions and address the potential for higher than expected substitution rates of naltrexone.PSD · Nov 2015
Cost-effectiveness
ICER values are redacted (shown as '****' in the document). The submission presented a cost-utility analysis versus placebo and a cost-minimisation analysis versus naltrexone, but the specific ICER figures are commercially sensitive.
The PBAC considered that the claim of superior comparative effectiveness over placebo was reasonable, however considered that the clinical relevance of this was unknown. PBAC · 2015
Decision context
PopulationAdults aged ≥18 years with alcohol use disorder (DSM-V) with an average daily alcohol consumption of >60g for men and >40g for women, who have failed to achieve adequate response to psychosocial intervention for at least 2 weeks, without physical withdrawal syndrome, not requiring immediate detoxification, and able to undergo concurrent psychosocial intervention.
Why it was knocked back
- uncertain clinical relevance of efficacy, inappropriate comparator weighting (one-third assumption not justified), concerns about trial population not reflective of PBS population (excluded mental health comorbidities), questions about non-inferiority to naltrexone, uncertain cost-minimisation assumptions
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2015 | Not recommended | placebo (with psychosocial intervention); naltrexone (secondary comparator) | — | RCT · Change from baseline in total alcohol consumption and number of heavy drinking days per month |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| SENSE | Ph 3 | 665 | Number of Patients With Adverse Events (AEs) | completed |
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both specify identical inclusion criteria: AUD, >60g/>40g daily alcohol, failed psychosocial intervention ≥2 weeks, concurrent psychosocial support, excluding physical withdrawal/detoxification need.